Stoler D L, Anderson G R, Russo C A, Spina A M, Beerman T A
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.
Cancer Res. 1992 Aug 15;52(16):4372-8.
Normal rat fibroblasts exhibit a staged response to anoxia which in several respects parallels processes activated in malignant tumor cells. We describe here a new element of the anoxic response, the induction by anoxia of a sequestered endonuclease activity. Such activity is elevated approximately 3-fold within anoxic fibroblasts and during Hirt DNA isolation is able to digest chromatin to produce a nucleosomal ladder. However, DNA is not measurably affected within intact cells, and cells retain complete viability as the endonuclease is induced. The anoxia-inducible endonuclease acts without specificity for DNA sequence. Trace leakage of this endonuclease into the nucleus has obvious potential to underlie the known propensity of anoxic cells to undergo amplification and may be associated with the break-related genomic instability of cancer cells.
正常大鼠成纤维细胞对缺氧表现出阶段性反应，这在几个方面与恶性肿瘤细胞中激活的过程相似。我们在此描述缺氧反应的一个新要素，即缺氧诱导的一种隐蔽性核酸内切酶活性。这种活性在缺氧成纤维细胞内升高约3倍，并且在Hirt DNA分离过程中能够消化染色质以产生核小体阶梯。然而，完整细胞内的DNA未受到可测量的影响，并且随着核酸内切酶的诱导，细胞保持完全的活力。缺氧诱导的核酸内切酶对DNA序列无特异性作用。这种核酸内切酶微量泄漏到细胞核中显然有可能成为缺氧细胞进行扩增的已知倾向的基础，并且可能与癌细胞的断裂相关基因组不稳定性有关。
